The pathogenesis of acute, latent and reactivated herpes simplex virus (HSV) of the peripheral autonomic nervous system is to be investigated using 3 approaches: 1) an in vivo model of infection of the superior cervical ganglion (SCG) in the mouse, 2) an in vitro model using dissociated neurons derived from the SCG of the rat, and 3) recovery of latent HSV from autonomic ganglia of humans. Particular attention will be directed at the way in which systemic host resistance, including immune defenses, and intrinsic metabolic alterations in ganglion cells are able to modulate the course of ganglionic infection.